The cardiac adaptation to pregnancy is characterized by ventricular enlargement without hypertrophy, while the cardiac response to hypertension is hypertrophy without enlargement. We propose that, in pregnancy-induced hypertension in humans, these two divergent influences produce a spectrum of ventricular morphology and function ranging from small, thick ventricles with supernormal function to large, thin ventricles with reduced function. Preliminary studies show that estrogen administration to the ewe simulates many of the cardiovascular adaptations of pregnancy, including rapid cardiac enlargement. This provides for a convenient model to study the mechanisms for cardiac adaptations during hypertensive pregnancy. We will use chronically instrumented ewes given estrogen to study the separate effects of enlargement, hypertension, and their interaction on cardiac function, contractility, and morphometry. We hypothesize that ventricular response are sensitive to the chronology and intensity of each stimulus. We predict that, when moderate hypertension is superimpose on established estrogen- induced cardiac enlargement, left ventricular function will deteriorate and cardiomyopathy amy result. We will test the hypothesis that prior treatment with estrogen inhibits the normal hypertrophic response to hypertension and that estrogen-induced enlargement renders the ventricle more susceptible to the deleterious effects of elevated arterial pressure on function, because of unfavorable geometry. Conversely, we predict that established hypertrophy from hypertension will inhibit cardiac enlargement by estrogen, resulting in preserved left ventricular function and contractility. In vivo methodology will include: measurement of high fidelity left ventricular pressure, minor axis dimension, wall thickness, and stroke volume by electromagnetic flow sensor. From these measurements, we will construct: function curves relating stroke volume to filling pressure, stroke volume-arterial pressure relations, fractional shortening-wall stress relations, and end systolic stress-end systolic dimension relations in order to determine the separate effects of arterial pressure, geometry and contractility on cardiac function. We will use morphometry to determine myocardial cell size, subcellular constituents, and interstitial fibrosis in order to detect the presence of hypertrophy and whether the response is physiologic or pathologic.